Experiments are directed toward understanding processes by which regulation of the immune system is controlled at the cellular level. The integrated roles of regulatory cells such as thymus-derived helper and suppressor T-cells are being defined. We are seeking to understand T-cell circuitry from the precursor stage through the various phenotypic stages between suppressor and helper functional stages. Our results involving the preferential inactivation of suppressor function of T-cells by natural microbial agents such as the streptococcal exotoxin, SPE, have delineated a novel approach towards understanding regulatory pathways and T-cell circuitry in the immune system. We have recently achieved stabilization of the helper T-cell phenotype as a functional T-cell hybridoma. Others being cloned appear to have other important activities. This approach is facilitating the ascertainment of definitive regulatory roles of T-cells. These monoclonal and functional T-cell clones also provide stable cellular targets for understanding the mechanisms of interference of microbes and their products in the immune system.